Acetylcholine in Mammalian Neuromuscular Transmission

Abstract

AFTER reviewing experimental results described in the literature, Acheson¹ came to the conclusion in 1948 that the amount of acetylcholine liberated by a single impulse at a presynaptic nerve terminal in muscle and sympathetic ganglia is probably of the order of 1.5 × 10⁻¹⁶ gm. (10⁻¹⁸ moles). He pointed out the large discrepancy between this quantity and the relatively large amounts (3 × 10⁻¹⁴ moles) hitherto found necessary for excitation when applied directly to the muscle. This discrepancy has been much reduced in recent years by the electrophoretic application of acetylcholine from micropipettes^3,7, and spikes have been produced in frog muscle fibres by this method with as little as 5.5 × 10⁻¹⁶ moles⁷. However, there still remained a substantial difference, and most of the potentials obtained by this method have not been strictly comparable with end-plate potentials elicited by nerve stimulation since they have a much slower time-course. For example, the quickest potential published by del Castillo and Katz³ rose to its maximum in 13 msec. These authors concluded that much faster potentials, and even greater sensitivity to acetylcholine, would be expected in the case of nervous release of acetylcholine, where the diffusion distance is less than 1µ ; in their experiments, the distance of the acetylcholine pipette from the end-plate was estimated to be 10–20µ(in a later paper⁴, they mention potentials with a rise time of 2–5 msec.).